Introduction: While myopericarditis due to Coxsackie virus-B has been widely reported, multi-organ involvement is rare. We report a unique case of Coxsackie B myopericarditis, which presented with rash, atypical pneumonia, hepatitis, and sepsis. Description: A previously healthy 32-year-old man presented to the emergency department in January 2022 endorsing shortness of breath, high-grade fever (39.2˚C), non-pruritic rash on extremities, vomiting, and diarrhea. He had tachypnea (24/min), hypoxia (SpO2 93% on air), and mild lymphadenopathy in the neck. Initial evaluation was pertinent for leukocytosis (17.8 thousand/µL) with neutrophil predominance (89.4%), elevated inflammatory markers (D-dimer [4390 ng/mL], procalcitonin [1.79 ng/mL], CRP [180.7 mg/L], lactate [3.19 mmol/L]), and transamnitis (AST: 160 U/L, ALT: 116 U/L); SARS-CoV-2 and blood cultures were negative. Chest imaging showed bibasilar consolidation, perihilar ground-glass nodules, and pericardial effusion; ultrasound showed acute hepatitis. He was empirically started on ceftriaxone and azithromycin. However, absence of clinical improvement, persistence of high-grade fever, and leukocytosis with low absolute CD3, CD4, and CD8 counts (286 cells/UL, 199 cells/UL and 71 cells/UL, respectively) suggested atypical infection; vancomycin and doxycycline were added. Further infection and autoimmune workup was negative. He developed atrial fibrillation and an echocardiogram was remarkable for ejection fraction of 50-55%, moderate pericardial effusion circumferential to the heart, and minimal collapse of the right atrium. On subsequent testing, Coxsackie virus B type 3 IgM was positive (1:320, reference 1:10). All antibiotics were discontinued, and the patient was managed with diltiazem, colchicine, ibuprofen, and supportive care; anticoagulation was not initiated. After a remarkable improvement in symptoms and rash, he was discharged home. Follow-up imaging showed resolution of bibasilar consolidations and pericardial effusion. Discussion: The likely mechanism of Coxsackie virus B–induced damage to myocytes (and possibly multi-organ involvement) is immune-mediated and direct viral cytotoxicity. Our patient’s atypical pneumonia responded well to colchicine and ibuprofen. A high index of suspicion is warranted.